Uniform expression and isotopic enrichment of multiple constructs of the fusion domain of hemagglutinin has been achieved, resulting in samples that are reasonably homogeneous (>70%) and suitable for NMR structural studies. Prior work on this system, primarily by Tamm and co-workers (U. of Virginia) was based primarily on NOE data and yielded relatively low resolution data without a clear view of the structural transition underlying the switch to fusion. To enhance the resolution, we need to record residual dipolar coupling, which requires a liquid crystalline medium compatible with detergents that are needed to solubilize the fusion domains. A suitable liquid crystalline medium has been developed for this purpose, consisting of the potassium salt of the dinucleotide d(GpG), which is compatible with detergents commonly used for solubilizing membrane proteins, including dodecylphosphocholine, the lysolipid 1 palmitoyl-2-hydroxy-sn-glycero-3-phosphocholine, and small bicelles consisting of dihexanoyl phosphatidylcholine and dimyristoyl phosphatidylcholine. The chiral nematic liquid crystalline phase of d(GpG) consists of long columns of stacked G-tetrad structures, and carry a net negative charge. For water-soluble systems, the protein alignment induced by d(GpG) is very similar to that observed for liquid crystalline Pf1 bacteriophage, but of opposite sign. Alignment of the detergent-solubilized fusion domain of hemagglutinin is demonstrated to be homogeneous and stable, resulting in high quality NMR spectra suitable for the measurement of residual dipolar couplings (RDCs). Structures derived from the new data for the monomeric form of the fusion domain show many similarities but also distinct differences relative to those of earlier studies.